Once considered rare, acute megakaryoblastic leukemia (AMKL) now accounts for about 12% of all cases of de novo acute myeloid leukemia in children. Most cases of AMKL are difficult to diagnose because of their complex clinical presentation and unusual bone marrow morphologic features. In children, AMKL is often confused with metastatic solid tumors or myelodysplastic syndrome. Between January 1984 and December 1999, 43 patients were diagnosed with childhood AMKL at the authors' institution. Five of these presented with unusual skeletal lesions. These abnormalities (bilaterally symmetrical periostitis and osteolytic lesions) differed markedly from those commonly reported in association with pediatric acute leukemias. The authors present their experience and review the literature to define the spectrum of bony involvement associated with AMKL. This report will contribute to the evolving clinical characterization of this entity and increase clinicians' and radiologists' awareness of the manifestations of AMKL.